Zanubrutinib Plus R-CHOP for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Non-GCB/ABC Diffuse Large B-Cell Lymphoma Clinical Trial

Official title:

Zanubrutinib Combination With R-CHOP in Treating Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04835870
• Other study ID #: ZR-CHOP
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2021
• Est. completion date: October 1, 2025

Study information

• Verified date: March 2022
• Source: The First Affiliated Hospital of Soochow University
• Contact: Caixia Li, M.D
• Phone: +86 512 67781856
• Email: licaixia[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim of this study will evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP for newly diagnosed untreated Non-GCB DLBCL Patients

Description:

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. According to Hans' algorithms, DLBCL can be identified as 2 subtypes: germinal b-cell-like(GCB) and non-germinal b-cell-like(non-GCB). Approximately 50 to 60% of DLBCL was non-GCB subtype DLBCL.The non-GCB DLBCL revealed poor clinical outcomes. Bruton's tyrosine kinase (BTK) inhibitors have established therapeutic activity in B cell malignancies, with potential activity in non-GCB DLBCL. This study will evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP for newly diagnosed untreated Non-GCB DLBCL Patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: October 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed Non-GCB DLBCL with extrinsic involvement

2. Age = 18 years

3. Measurable disease of at least 15mm(node)/10mm(extranodal)

4. ECOG performance status 0-2

5. Adequate organ function:Cardiac ejection fraction (EF) = 50%;Creatinine clearance rate (=30 mL/min) of serum creatinine; Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) =3 times ULN

6. Adequate bone marrow function:Platelet count (= 50×10^9/L);Hemoglobin (= 8 g/dL);The absolute value of neutrophils (=1.0×10^9/L)

7. Estimated survival time =3 months

8. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study

Exclusion Criteria:

1. Accepted major surgery within 4 weeks before treatment;

2. Diagnosis of primary mediastinal lymphoma or primary CNS lymphoma;

3. Previous history of indolent lymphoma;

4. Prior malignancy (other than DLBCL), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer ?malignant tonsilloma or carcinoma in situ;

5. History of intracranial haemorrhage in preceding 6 months,requires or receiving anticoagulation with warfarin or equivalent antagonists;

6. Requires treatment with a strong/medium CYP3A inducer;

7. The previous use of anthracycline-based drugs > 150 mg/m2;

8. Evidence of complications or medical conditions, including but not limited, that may interfere the conduct of the study or place the patient at serious risk:significant cardiovascular disease(class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification?myocardial infarction within 6 months of screening?uncontrolled or symptomatic arrhythmias) and/or significant lung disease;

9. HIV infection and/or active hepatitis B or active hepatitis C;

10. Uncontrolled systemic infection;

11. Pregnant or breasting-feeding women;

12. According to the researchers' judgment, patients' underlying condition may increase their risk of receiving research drug treatment, or confuse their judgment on toxic reactions.

Related Conditions & MeSH terms

• Lymphoma, Large B-Cell, Diffuse
• Non-GCB/ABC Diffuse Large B-Cell Lymphoma

Intervention

Drug:
• Zanubrutinib
Zanubrutinib-160mg bid PO d0-d20(1-21d)
• Rituximab
Rituximab-375 mg/m2 i.v d0 (/21d)
• Cyclophosphamide
Cyclophosphamide-750 mg/m2 i.v d1 (/21d)
• Doxorubicin
Doxorubicin-50 mg/m2 i.v d1 (/21d)
• Vincristine
Vincristine-1.4 mg/m2 i.v d1 (/21d)(2 mg max)
• Prednisone
Prednisone-100 mg p.o d1-d5 (/21d)

Locations

Country	Name	City	State
China	The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital of USTC Anhui Provincial Hospital	Hefei	Anhui
China	Shandong Provincial Hospital Affiliated to Shandong First Medical University	Jinan	Shandong
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Changshu No.1 People's Hospital	Suzhou	Jiangsu
China	Suzhou Hongci Hematology Hospital	Suzhou	Jiangsu
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Zhangjiagang First Peoples Hospital	Suzhou	Jiangsu
China	Affiliated Hospital Of Jiangnan University	Wuxi	Jiangsu
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Xuzhou Central Hospital	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival(PFS)	To measure the duration of response to ZR-CHOP over a follow-up period of 18 months	up to 18 months
Secondary	Overall Response Rate (ORR)	To measure the duration of response to ZR-CHOP over a follow-up period of 18 months	up to 18 months
Secondary	Complete Response Rate	Number of patients who achieved complete response after treatment by ZR-CHOP	up to 18 months
Secondary	Duration of Response	Duration of overall response will be assessed from the first ZR-CHOP given to progression,death or last follow-up.	up to 18 months
Secondary	Overall Survival	OS will be assessed from the first ZR-CHOP given to death or last follow-up.	up to 18 months
Secondary	Adverse events profile	Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated	Measured from start of treatment until 28 days after last dose